Project Summary Research on hearing loss and tinnitus associated with neurotoxic chemotherapy (CTX) has focused primarily on pediatric patients. In adults, the extremely limited amount of work has reported on hearing loss and tinnitus associated with the administration of platinum compounds primarily in patients undergoing active treatment for testicular or head and neck cancer. However, no studies have systematically evaluated hearing loss and tinnitus in cancer survivors who received a platinum and/or a taxane compound for breast, gastrointestinal (GI), gynecological (GYN), or lung cancer. Given that these diagnoses are the four most common cancers in adults and platinum and taxane compounds are the mainstay of treatment for these cancers, an evaluation of the severity and impact of hearing loss and tinnitus from these drugs is a significant issue for cancer survivorship. Recently, we completed enrollment in our ongoing R01 (CA151692) that is focused on an evaluation of differences in phenotypic and molecular characteristics of chemotherapy-induced neuropathy (CIN) in 400 survivors with CIN and 200 survivors without CIN. In preliminary analyses data from 310 patients with CIN, 49.0% reported hearing loss and/or tinnitus (i.e., 16.1% reported only hearing loss, 12.3% reported only tinnitus, and 20.6% reported both hearing loss and tinnitus). In contrast, in the 79 patients without CIN, 72.2% did NOT report hearing loss or tinnitus. Given that almost 50% of the patients with CIN reported some form of auditory toxicity, this grant application will focus on a more detailed characterization of hearing loss and tinnitus to determine their underlying mechanisms and impact of survivors' level of function and QOL. Blood samples will be collected and stored for future genomic analyses. The primary aims of this study, in a sample of survivors who received a platinum and/or a taxane compound and are classified into one of four groups (i.e., 1) survivors without CIN, hearing loss, and tinnitus; 2) survivors with CIN and without hearing loss and tinnitus; 3) survivors with CIN and only hearing loss; and 4) survivors with CIN and both hearing loss and tinnitus), are to: 1) evaluate for differences among the four groups in subjective and objective characteristics of hearing loss; 2) evaluate for differences among the four groups in subjective characteristics of tinnitus; and 3) evaluate for differences among the four groups in functional status, cognitive status, financial toxicity, and QOL. The secondary aim of this study is to evaluate for changes over time in subjective and objective measures of CIN in the survivors with CIN who were evaluated in CA151692. The information on etiology and severity, as well as on the impact of these two types of auditory toxicity will be used to plan intervention studies to improve hearing, reduce the impact of tinnitus, and assist cancer survivors to adapt to the long term effects of hearing loss and tinnitus.